Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1

Heli Liu; Z. Sean Juo; Ann Hye Ryong Shim; Pamela J. Focia; Xiaoyan Chen; K. Christopher Garcia; Xiaolin He

doi:10.1016/j.cell.2010.07.040

Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1

Heli Liu, Z. Sean Juo, Ann Hye Ryong Shim, Pamela J. Focia, Xiaoyan Chen, K. Christopher Garcia, Xiaolin He^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

128 Scopus citations

Abstract

Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1, and A39R is a Sema7A mimic secreted by smallpox virus. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1. Both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers, in which the Semaphorin and PlexinC1 β propellers interact in an edge-on, orthogonal orientation. Both binding interfaces are dominated by the insertion of the Semaphorin's 4c-4d loop into a deep groove in blade 3 of the PlexinC1 propeller. A39R appears to achieve Sema7A mimicry by preserving key Plexin-binding determinants seen in the mammalian Sema7A complex that have evolved to achieve higher affinity binding to the host-derived PlexinC1. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization.

Original language	English (US)
Pages (from-to)	749-761
Number of pages	13
Journal	Cell
Volume	142
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2010.07.040
State	Published - Sep 3 2010

Funding

We thank the staff at the LS-CAT beamlines at APS and the staffs of ALS and SSRL for the support in X-ray data collection. We also thank L. Colf, and N. Goriatcheva for help with the expression of A39R. X.H. is supported by the NIH grant 1R01GM07805, and K.C.G. is an Investigator of the Howard Hughes Medical Institute and is supported by NIH-R01-AI51321. The Structural Biology Facility is supported by the R.H. Lurie Comprehensive Cancer Center of Northwestern University.

Keywords

Molneuro
Proteins

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2010.07.040

Cite this

@article{8a54e75e3dc948f79d219e9dc70bd7e0,

title = "Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1",

abstract = "Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1, and A39R is a Sema7A mimic secreted by smallpox virus. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1. Both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers, in which the Semaphorin and PlexinC1 β propellers interact in an edge-on, orthogonal orientation. Both binding interfaces are dominated by the insertion of the Semaphorin's 4c-4d loop into a deep groove in blade 3 of the PlexinC1 propeller. A39R appears to achieve Sema7A mimicry by preserving key Plexin-binding determinants seen in the mammalian Sema7A complex that have evolved to achieve higher affinity binding to the host-derived PlexinC1. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization.",

keywords = "Molneuro, Proteins",

author = "Heli Liu and Juo, {Z. Sean} and Shim, {Ann Hye Ryong} and Focia, {Pamela J.} and Xiaoyan Chen and Garcia, {K. Christopher} and Xiaolin He",

note = "Funding Information: We thank the staff at the LS-CAT beamlines at APS and the staffs of ALS and SSRL for the support in X-ray data collection. We also thank L. Colf, and N. Goriatcheva for help with the expression of A39R. X.H. is supported by the NIH grant 1R01GM07805, and K.C.G. is an Investigator of the Howard Hughes Medical Institute and is supported by NIH-R01-AI51321. The Structural Biology Facility is supported by the R.H. Lurie Comprehensive Cancer Center of Northwestern University. ",

year = "2010",

month = sep,

day = "3",

doi = "10.1016/j.cell.2010.07.040",

language = "English (US)",

volume = "142",

pages = "749--761",

journal = "Cell",

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T1 - Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1

AU - Liu, Heli

AU - Juo, Z. Sean

AU - Shim, Ann Hye Ryong

AU - Focia, Pamela J.

AU - Chen, Xiaoyan

AU - Garcia, K. Christopher

AU - He, Xiaolin

N1 - Funding Information: We thank the staff at the LS-CAT beamlines at APS and the staffs of ALS and SSRL for the support in X-ray data collection. We also thank L. Colf, and N. Goriatcheva for help with the expression of A39R. X.H. is supported by the NIH grant 1R01GM07805, and K.C.G. is an Investigator of the Howard Hughes Medical Institute and is supported by NIH-R01-AI51321. The Structural Biology Facility is supported by the R.H. Lurie Comprehensive Cancer Center of Northwestern University.

PY - 2010/9/3

Y1 - 2010/9/3

N2 - Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1, and A39R is a Sema7A mimic secreted by smallpox virus. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1. Both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers, in which the Semaphorin and PlexinC1 β propellers interact in an edge-on, orthogonal orientation. Both binding interfaces are dominated by the insertion of the Semaphorin's 4c-4d loop into a deep groove in blade 3 of the PlexinC1 propeller. A39R appears to achieve Sema7A mimicry by preserving key Plexin-binding determinants seen in the mammalian Sema7A complex that have evolved to achieve higher affinity binding to the host-derived PlexinC1. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization.

AB - Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1, and A39R is a Sema7A mimic secreted by smallpox virus. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1. Both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers, in which the Semaphorin and PlexinC1 β propellers interact in an edge-on, orthogonal orientation. Both binding interfaces are dominated by the insertion of the Semaphorin's 4c-4d loop into a deep groove in blade 3 of the PlexinC1 propeller. A39R appears to achieve Sema7A mimicry by preserving key Plexin-binding determinants seen in the mammalian Sema7A complex that have evolved to achieve higher affinity binding to the host-derived PlexinC1. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization.

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JO - Cell

JF - Cell

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ER -

Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1

Abstract

Funding

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ASJC Scopus subject areas

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Molecular mechanism of guidance cue recognition

Molecular mechanism of guidance cue recognition

Molecular mechanism of guidance cue recognition

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Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

Molecular mechanism of guidance cue recognition

Molecular mechanism of guidance cue recognition

Molecular mechanism of guidance cue recognition

Cite this